This invention relates to a treatment for psoriasis and specifically to a composition containing one or more compounds which have been found to be effective when topically applied, to improve and heal the skin lesions of psoriasis in humans.
Psoriasis is a chronic disease, and remains a disfiguring and disabling cutaneous impairment to millions of persons. Its etiology is completely unknown, and therefore prevention remains inconceivable. Therapy has necessarily been empiric, and has included the systemic use of antimitotic drugs such as methotrexate to induce remissions of the lesions. However, acute and chronic toxicity on tissues other than skin has discredited use of methotrexate. Therefore it is imperative that other means of therapy be found by external delivery of drugs so that toxicity is confined chiefly to the skin, or by the discovery of new drugs having nontoxic attributes.
In our prior patent application entitled TREATMENT OF PSORIASIS, Ser. No. 371,516, filed June 19, 1973, now U.S. Pat. No. 3,904,766, we described and claimed the use of mechlorethamine hydrochloride ointment in the treatment of psoriasis by topical application. We also described that in an oil base the compound formed a stable composition.
Prior to our above invention mechlorethamine hydrochloride, a nitrogen mustard, had been generally discounted as a treatment for psoriasis because, in effective dosages a high percentage of patients became sensitized. In addition, the compound proved to be highly unstable in an aqueous solution and rapidly degraded to what was considered an ineffective byproduct by those skilled in the art.
The treatment described in our above application, however, was necessarily proceeded by inducing an immunological tolerance so that the patient would not be susceptible to a delayed hypersensitive reaction. The procedure for inducing immune tolerance included weekly intraveneous injections of 0.2 milligrams of mechlorethamine hydrochloride in an aqueous solution over at least a three week period prior to initiation of topical therapy.
In our prior patent application Ser. No. 455,665, filed March 28, 1974, now U.S. Pat. No. 3,920,840, we described and claimed our discovery that psoriatic conditions could be successfully treated by utilizing one of the degradation products of mechlorethamine hydrochloride, N-methyldiethanolamine, a compound which is not primarily either antimitotic nor allergic. This compound was found to be essentially nontoxic to both animals and humans when used as a topical agent in a therapeutic composition containing from 0.5 to 5 percent by weight thereof. The compound also caused no detectable signs of any irritation to human skin.
In our parent patent application entitled TREATMENT OF PSORIASIS WITH 6-AMINONICOTINAMIDE AND THIONICOTINAMIDE, Ser. No. 601,411, filed Aug. 4, 1975, we describe and claim the use of 6-aminonicotinamide and thionicotinamide in the treatment of psoriasis by topical application.
Although 6-aminonicotinamide showed no toxic signs when topically applied to the skin of humans or animals, this compound did exhibit various symptoms of toxicity in animals when administered systemically at a dose of 40 mg/kg. Another shortcoming with this compound in a topical treatment of psoriasis is its potential irritability to psoriatic skin. In patients having greater than 20% of their skin involved with psoriatic lesions 6-aminonicotinamide on topical application appeared to irritate the lesion and therefore exacerbate the disease. Thionicotinamide is a relatively nontoxic substance. However, its irritability to psoriatic skin is even greater than that of 6-aminonicotinamide.